1,214 research outputs found
Anaesthetic Preconditioning; The Role of ATP-Sensitive K+ Channels
Stroke in general but especially in the postoperative period is a serious clinical
problem that warrants new therapeutic approaches. Here neuroprotective
strategies and especially preconditioning have recently emerged as promising.
Preconditioning was originally demonstrated in the heart but was subsequently
also found in other organs. Classically it describes a phenomenon where short
periods of ischaemia render tissues less vulnerable to major infarcts. In addition to
ischaemia neuronal preconditioning can be achieved pharmacologically as well as
through inhalational anaesthetics or drugs that open ATP-sensitive K+(KATP)
channels. However, the mechanisms through which anaesthetics produce
protection remain elusive and the use of K+ channel openers is hampered by their
inability to cross the blood-brain-barrier.
This study was conducted to investigate the effects of inhalational anaesthetics on
KATP
channels and to explore whether their neuronal preconditioning properties
were dependent on KATP channel opening. First, in whole-cell and excised patchclamp
experiments the effects of inhalational anaesthetics on recombinant wild
type neuronal (Kir6.2/SUR1) KATP and related as well as modified channels were
evaluated. Secondly, the KATP channel dependence of anaesthetic preconditioning
was tested in neuronal-glial co-cultures.
Recombinant KATP channels were activated by xenon, but inhibited by
halogenated volatiles. Moreover, it was shown that xenon acted directly on the
Kir6.2 pore-forming subunit, reduced the ability of ATP to inhibit the channel and
had no effect on the ATP-regulated Kir1.1 channel. Functionally both sevoflurane
and xenon preconditioned neurons at clinically used concentrations but only the
effect of xenon was dependent on KATP channel activation.
Thus this study established xenon as a novel KATP channel opener. It interacts
with the pore-forming Kir6.2 rather than the regulatory sulphonylurea receptor
subunit and disinhibits the channel from the blocking actions of ATP. As a
consequence xenon but not sevoflurane is able to precondition neurons in a KATP
channel-dependent manner
Cell death in sepsis: a matter of how, when, and where
Dysregulated cell death in several tissues is intimately involved in the pathogenesis of sepsis and contributes to multiple organ failure. Whether cell death during sepsis occurs by necrosis or apoptosis may depend on the cell type as well as the disease stage and is therefore a matter of intense debate. While lymphocyte apoptosis contributes to immunosuppression in sepsis, recent evidence suggests that necrosis of hepatocytes predominates in septic patients with liver dysfunction and correlates with poor survival. These distinct modes of cell death might have different consequences for the inflammatory response but are also critical for therapeutic interventions and the disease outcome. Understanding the complexity of death processes employing recently available serum biomarkers of cell death could lead to novel therapeutic approaches and assist in the steering of sepsis treatment
Gravitation Physics at BGPL
We report progress on a program of gravitational physics experiments using
cryogenic torsion pendula undergoing large-amplitude torsion oscillation. This
program includes tests of the gravitational inverse square law and of the weak
equivalence principle. Here we describe our ongoing search for
inverse-square-law violation at a strength down to of standard
gravity. The low-vibration environment provided by the Battelle Gravitation
Physics Laboratory (BGPL) is uniquely suited to this study.Comment: To be published in The Proceedings of the Francesco Melchiorri
Memorial Conference as a special issue of New Astronomy Review
Mechanisms of Cell Death in Acute Liver Failure
Acute liver failure (ALF) can be the consequence of various etiologies, that might vary between different geographic regions. Most frequent are intoxications with acetaminophen, viral hepatitis, or liver damage of unknown origin. ALF occurs when the extent of hepatocyte death exceeds the regenerative capacity of the liver. The mode of liver cell death that is predominantly induced in ALF, i.e., apoptosis or necrosis, is still controversial and presumably determined by the etiology, duration, and magnitude of liver injury. Severe liver damage involves oxidative stress and depletion of ATP resulting in necrosis. In contrast, maintenance of ATP stores is required for the execution of apoptosis. Recent data suggest that necrosis resulting from severe liver damage is associated with poor outcome of ALF patients. Discrimination between apoptosis and necrosis might be therefore useful for the identification of ALF patients requiring liver transplantation. Identification of the molecular cell death mechanisms remains an important issue not only for early prediction of ALF outcome, but also for therapeutic interventions. In view of the pleiotropic functions of critical mediators of cell death and tissue regeneration, a particular challenge will be to reduce hepatocellular death without inhibiting the regenerative capacity of the liver. Here, we review the molecular mechanisms of hepatocyte injury and the pathways leading to apoptosis and necrosis, which might represent potential diagnostic and therapeutic targets in ALF
Taste Preference Assay for Adult Drosophila
Olfactory and gustatory perception of the environment is vital for animal survival. The most obvious application of these chemosenses is to be able to distinguish good food sources from potentially dangerous food sources. Gustation requires physical contact with a chemical compound which is able to signal through taste receptors that are expressed on the surface of neurons. In insects, these gustatory neurons can be located across the animal's body allowing taste to play an important role in many different behaviors. Insects typically prefer compounds containing sugars, while compounds that are considered bitter tasting are avoided. Given the basic biological importance of taste, there is intense interest in understanding the molecular mechanisms underlying this sensory modality. We describe an adult Drosophila taste assay which reflects the preference of the animals for a given tastant compound. This assay may be applied to animals of any genetic background to examine the taste preference for a desired soluble compound
Finite Element Modeling for the Structural Analysis of Al-Cu Laser Beam Welding
AbstractLaser beam welding of aluminum and copper (Al-Cu) materials is a cost efficient joining technology to produce e.g. connector elements for battery modules. Distortion low connections can be achieved, which have electrical favorable properties. Numerical simulation of the laser beam welding process of Al-Cu dissimilar materials can provide further insight into principal process mechanisms and mechanical response of the joint parts. In this paper a methodology is introduced to investigate the structural behavior of Al-Cu joints in overlap joint with respect to welding distortions and residual stresses. First the material model of the homogeneous base materials are validated. Next, a generic material model approach is used to simulate the structural behavior of heterogeneous Al-Cu connections
Laboratory Tests of Gravitational Physics Using a Cryogenic Torsion Pendulum
Progress and plans are reported for a program of gravitational physics
experiments using cryogenic torsion pendula undergoing large amplitude
torsional oscillation. The program includes a UC Irvine project to measure the
gravitational constant G and joint UC Irvine - U. Washington projects to test
the gravitational inverse square law at a range of about 10 cm and to test the
weak equivalence principle.Comment: 17 pages, 11 figures, contribution to the 10th Marcel Grossman
Conference Proceedings (Rio de Janeiro, July 20 - 26, 2003) - changed wording
in first paragraph of section
Is number sense impaired in chronic pain patients?
BACKGROUND: Recent advances in imaging have improved our understanding of the role of the brain in painful conditions. Discoveries of morphological changes have been made in patients with chronic pain, with little known about the functional consequences when they occur in areas associated with ‘number-sense’; thus, it can be hypothesized that chronic pain impairs this sense. METHODS: First, an audit of the use of numbers in gold-standard pain assessment tools in patients with acute and chronic pain was undertaken. Secondly, experiments were conducted with patients with acute and chronic pain and healthy controls. Participants marked positions of numbers on lines (number marking), before naming numbers on pre-marked lines (number naming). Finally, subjects bisected lines flanked with ‘2’ and ‘9’. Deviations from expected responses were determined for each experiment. RESULTS: Four hundred and ninety-four patients were audited; numeric scores in the ‘moderate’ and ‘severe’ pain categories were significantly higher in chronic compared with acute pain patients. In experiments (n=150), more than one-third of chronic pain patients compared with 1/10th of controls showed greater deviations from the expected in number marking and naming indicating impaired number sense. Line bisection experiments suggest prefrontal and parietal cortical dysfunction as cause of this impairment. CONCLUSIONS: Audit data suggest patients with chronic pain interpret numbers differently from acute pain sufferers. Support is gained by experiments indicating impaired number sense in one-third of chronic pain patients. These results cast doubts on the appropriateness of the use of visual analogue and numeric rating scales in chronic pain in clinics and research
Interventions for increasing uptake in screening programmes
Introduction: Opportunities for the early detection of disease are not sufficiently being taken advantage of. Specific interventions could increase the uptake of prevention programmes. A comprehensive analysis of effectiveness and cost-effectiveness of these interventions with reference to Germany is still needed. Objectives: This report aimed to describe and assess interventions to increase uptake in primary and secondary prevention and to explore the assessment of their cost-effectiveness. Methods: 29 scientific databases were systematically searched in a wide strategy. Additional references were located from bibliographies. All published systematic reviews and primary studies were assessed for inclusion without language restrictions. Teams of two reviewers identified the literature, extracted data and assessed the quality of the publications independently. Results: Four HTA reports and 22 systematic reviews were identified for the medical evaluation covering a variety of interventions. The economic evaluation was based on two HTA-reports, one meta-analysis and 15 studies. The evidence was consistent for the effectiveness of invitations and reminders aimed at users, and for prompts aimed at health care professionals. These interventions were the most commonly analysed. (Financial) Incentives for users and professionals were identified in a small number of studies. Limited evidence was available for cost-effectiveness showing incremental costs for follow-up reminders and invitations by telephone. Evidence for ethical, social and legal aspects pointed to needs in vulnerable populations. Discussion: The material was heterogeneous regarding interventions used, study populations and settings. The majority of references originated from the United States and focused on secondary prevention. Approaching all target groups by invitations and reminders was recommended to increase uptake in prevention programmes in general. Conclusions: Further research should aim to focus on primary prevention. Future research should also focus on specific interventions aiming to include vulnerable target groups and individuals, who have not previously made use of opportunities for prevention
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